tbuckley/cabot-search huggingface dataset:
IMG-12. Transient atypical brain and spine MRI features after high-dose chemotherapy may represent clumps of CD34+ hematopoietic stem cells
Authors: Antonia Ramaglia, Elena Arkhangelskaya, Angela Rita Sementa, Giovanni Morana, Andrea Rossi, Maura Faraci, Gianluca Piccolo, Marco Crocco, Claudia Milanaccio, Maria Luisa Garrè, Antonio Verrico
Journal: Neuro-Oncology (2022)

Abstract High-dose chemotherapy is a therapeutic option in selected cases of pediatric high-grade brain tumor (pHGBT). Following high-dose chemotherapy, bone marrow is reconstituted by means of CD34+ peripheral blood stem cell (PBSC) infusion. Intravenously injected PBSCs have been reported to migrate to the Central Nervous System (CNS) and to persist for weeks. We report two cases of pHGBT in which, following PBSC infusion, we observed peculiar brain MRI signal alterations suggestive of clumps of CD34+ cells. A 15-month-old female underwent surgery and chemotherapy for an infratentorial, non-disseminated, Atypical Teratoid Rhabdoid Tumor. Following the second course of high-dose chemotherapy, MRI excluded residual disease, but revealed two contrast-enhancing nodules in the supratentorial ventricular system, with no evidence of diffusion restriction, unlike the primary tumor. Cerebrospinal fluid was collected by means of lumbar puncture and centrifuged: no neoplastic cells were found, while a few cells were positive when immunostained with anti-CD34 antibody. As no disease progression was documented, the patient completed her treatment with focal radiotherapy. Three months after the end of therapy, MRI showed new enhancing nodules with restricted diffusion, in keeping with leptomeningeal spread of disease; these progressively increased in size, despite subsequent lines of treatment, while the above-mentioned ventricular nodules shrank. Similar transient alterations were detected in a 4-year-old boy who had received treatment for high-risk Medulloblastoma, including high-dose chemotherapy. CONCLUSIONS: In the setting of new enhancing brain and spine findings with atypical MRI features, after high-dose chemotherapy to treat pHGBT, the hypothesis of CNS homing of CD34+ hematopoietic stem cells should be considered in the differential diagnosis.
Epidemiological characteristics and cause-specific survival analysis of plasmablastic lymphoma (PBL) using the SEER database.
Authors: Dhairya Gor, Pranav Gwalani, Rajvi Gor, Kyle Wiseman, Michael J. Levitt, Shuvendu Sen
Journal: Journal of Clinical Oncology (2022)

e19546 Background: Plasmablastic lymphoma (PBL), a variant of diffuse large B-cell lymphoma, is a rare and aggressive malignancy. Minimal guidelines exist for its diagnosis and standard of care. Hence, we studied the epidemiological characteristics and survival variables of PBL patients by using the SEER 20 database. Methods: A total of 229 cases of PBL (WHO ICD-O-3 codes 9735/3) were identified between 2000 and 2015, after excluding 66 cases with unknown survival time or no microscopic confirmation. The epidemiological characteristics and the survival variables included were age, gender, ethnicity, Ann Arbor stage, B-symptoms, and site. The overall 5-year survival (OS), cause-specific 5-year survival (CSS), and cause-specific survival plots across different strata were plotted using the Kaplan Meier Method. The analysis was done using the Cox proportional hazard regression model (p &lt; 0.05). Results: The incidence of PBL was 0.03 per 100,000 cases. It was more common in adults less than 60 years (61.57%), males (79.04%), and White ethnicity (72.49 %). There were more cases of patients with advanced Ann Arbor stages (3 or 4) PBL (52.84%), although some patients (5.68%) had unknown staging. There were 55.02% of extranodal cases, and 28.38% of patients had B-symptoms. The OS was 36.55%, and the CSS was 46.5%. CSS did not differ significantly based on age, race, or gender. However, the absence of B-symptoms was associated with better CSS (HR: 0.654, 95% CI: 0.455-0.941, p: 0.022). Nodal involvement (HR: 1.553, 95% CI: 1.135-2.124, p: 0.006) and advanced stages 3 or 4 (HR: 1.414, 95% CI: 1.018-1.962, p: 0.038) were also linked to a poor CSS. Conclusions: PBL patients with a primary nodal involvement and advanced staging (3 or 4) had poor CSS, and the absence of B-symptoms was associated with a better outcome. Age, gender, and ethnicity had no discernible effects on survival. We did not include therapeutic options in our study, and hence, further studies analyzing the impact of treatment options on PBL survival can be conducted.[Table: see text]
Comparison of lung functions of normal and hypertensive individuals
Authors: F Oza Patel, HARITA Vyas, KRIMA Tanna
Journal: Cardiovascular Research (2022)

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Hypertension is a medical condition in which the blood pressure is chronically elevated. It normally refers to arterial hypertension. In past years, the diastolic value was emphasized in assessing HTN. However elevation SBP is also associated with increased incidence of coronary and cardiovascular diseases (e.g. stroke). Therefore both SBP and DBP value are important to note. Pulmonary function test measures the function of lung capacity and lung and chest wall mechanics to determine whether or not the patients have a lung problem. Lung functions tests are commonly referred as —PFTs||. When a patient is referred for PFTs, it means that a battery of tests may be carried out including: simple screening spirometry, static lung volume measurement, diffusing capacity of carbon monoxide, airway resistance, respiratory muscle strength and arterial blood gases. Forced vital capacity (FVC) is the maximum volume of air which can be exhales or inspired during forced maneuver. Forced expired volume in one second (FEV1) is the volume of air expired in the first second of maximal expiration after a full inspiration. The total volume of air that is exhaled during forced expiration is called FVC. It is the FEV1 expressed as percentage of FVC and give the clinically useful index of airflow limitation. The greatest flow rate achieved during forceful expiration are called Peak Expiratory Flow Rate (PEFR) and usually taken as an indicator of larger airway resistance. Aim To compare the lung functions of normotensive and hypertensive individuals. Methodology Study Design: Cross-sectional Study Study Duration: Total study duration was 6 months. Subjects: 30 subjects Sampling Design: Purposive sampling Procedure- Ethic's approval and written informed consent of the subjects was taken prior to study. Procedure and purpose of the study was explained to the participants. In this study male and female between age group of 35 to 65 years who were Non-smokers and willing to participate were included. Subjects who were Smokers or who had URTI, any cardio Respiratory Illness or Any major Neuromuscular or musculoskeletal disorders were excluded. Participants were divided into two groups: one who was having HTN and other who were normotensive. Outcome measures: FEV1 % of predicted FVC% of predicted PEFR% of predicted Results Statistical analysis was done by SPSS version 16.Mann-Whitney U test was applied to see difference of lung function in hypertensive and normotensive individuals. Pulmonary function test parameters in hypertensives were statistically significantly lesser than normal controls (p&amp;lt;0.05). Conclusion Lung functions of hypertensive individuals shows significant reduction as compared to the normotensive individuals. Thus, it can be concluded that persistent high blood pressure is responsible for altered pulmonary functions.
Video-assisted informed consent in endoscopic urology: A randomized trial on ureteroscopy
Authors: R. Malinaric, G. Mantica, F. Esperto, L. Cacciatore, S. Parodi, S. Tappero, G. Traversa, A. Salerno, F. Balzarini, R. Papalia, R.M. Scarpa, C. Terrone
Journal: European Urology (2022)
The addition of fludarabine to cyclophosphamide for lymphodepleting chemotherapy enhances the persistence of infused NY-ESO-1 TCR anticancer therapy TBI-1301.
Authors: Marcus O. Butler, Samuel Saibil, Valentin Sotov, Sarah Boross-Harmer, Elizabeth Scheid, Diana Gray, Brendan Van As, Aileen Trang, Kendra Ross, Pamela S. Ohashi, Shinya Tanaka, Shuichi Takahashi, Naoto Hirano
Journal: Journal of Clinical Oncology (2022)

2539 Background: Adoptive transfer of T cell receptor (TCR) gene-engineered T cells can induce durable anti-cancer responses. TBI-1301 is a novel gene therapy produced by engineering autologous lymphocytes to express an NY-ESO-1-specific TCR using a retrovirus vector that encodes siRNA to silence endogenous TCR. In this study, we examined a repeat infusion of TBI-1301 and the addition of fludarabine to cyclophosphamide for pre-infusion lymphodepletion. Methods: Eligibility included informed consent, HLA-A*02:01 or A*02:06 haplotype, and NY-ESO-1 expression by IHC. Eligible patients underwent harvest of PBMC which were processed at the treating site to generate engineered TBI-1301 cells. The study design infused 5x10 9 cells on day 0 and day 14 to patients following lymphodepletion with cyclophosphamide (CY; 750 mg/m 2 on day -7 and -6) plus fludarabine (FLU; 30 mg/m 2 on day -7 and -6). Repeat infusions were performed in two cohorts: Cohort B - patients who had previously received NY-ESO-1 TCR-transduced cells and Cohort C - NY-ESO-1 TCR treatment naïve patients. Endpoints included safety, efficacy, and biological correlates for persistence of NY-ESO-1-specific T cells post infusion. Results: Ten patients were enrolled in cohorts B and C. Nine patients in total are evaluable for response and toxicity, and no DLTs have been observed. In cohort B, 5 patients (5 synovial sarcoma) were treated, and 5 have received the target dose. In cohort C, 5 patients (3 synovial sarcoma, 2 melanoma) were treated, and 4 have received the target dose. One patient received a single infusion due to bacteremia on week 2. One of 5 patients in cohort B was previously treated with TBI-1301 cells in cohort C. In each cohort, 4 patients experienced grade 1-2 cytokine release syndrome. Best overall response by RECIST v1.1 was 3 stable disease, and 2 progressive disease in cohort B; and 2 stable disease and 2 progressive disease in cohort C. When compared to the earlier cohort, biomarker analysis demonstrated substantially longer persistence of transferred TBI-1301 cells in infused patients who received fludarabine (up to 372+ and 460+ days), and the cells displayed a less differentiated phenotype. Conclusions: Repeat infusions of TBI-1301 following lymphodepletion appears to be safe and to possess anti-tumor activity. Addition of FLU to the lymphodepletion regimen may contribute to longer persistence of gene-engineered T cells. Clinical trial information: NCT02869217.
Application of XCELSIOR, a nationwide real-world observational research protocol, to identify efficacious targeted therapy regimens in advanced pancreatic adenocarcinoma.
Authors: Timothy Joseph Stuhlmiller, Asher Wasserman, Zachariah Cole, Santosh Kesari, Mark Shapiro
Journal: Journal of Clinical Oncology (2022)

e16245 Background: The proliferation of multi-omic diagnostics, highly selective targeted therapies, multi-modal immunotherapies, and personalized vaccines has yielded many promising novel combination regimens. Still, many patients with advanced cancer are left without clear options because the clinical efficacy of these regimens is based on anecdotal evidence as collective learning from real world practice is uncoordinated across the US. XCLESIOR ( NCT03793088 ) is a nationwide observational research protocol designed to efficiently gather, centralize, and standardize electronic medical records from any institution in the country, permitting complete longitudinal histories to be compiled for individual patients and analyzed on aggregate. Methods: Patients with pancreatic carcinoma were e-consented to XCELSIOR and real world data was entered into a 21 CF Part 11-compliant database and source-verified from raw electronic medical records generated in the standard practice of medicine including physician clinic notes, radiology reports, lab testing values, and genomics reports. Time-on-treatment and overall survival (OS) were calculated for cohorts based on treatment regimens containing chemotherapy, immunotherapy, or molecularly-targeted therapy. Results: As of February 1 st , 2022, a total of 330 patients (pts) with pancreatic carcinoma had consented to XCELSIOR representing 199 institutions or oncology practices. 195 pts with metastatic pancreatic adenocarcinoma had longitudinal data structured and suitable for analysis at time of writing. Median follow-up from diagnosis was 1.3 years. The most prevalent treatment regimens were FOLFIRINOX (154 pts) and gemcitabine/nab-paclitaxel (139 pts). 28 pts were treated with targeted therapies and had significantly longer OS than pts that were never treated with targeted therapies (2.6 vs. 1.1 years median OS). Targeted therapies were most commonly employed at 3 rd line (15/28) and 4 th line (7/28), suggesting they benefitted pts following SOC chemotherapeutic regimens. Molecular targeted therapies utilized included primarily PARP inhibitors, MAPK pathway inhibitors, and HER2-targeted therapies. Time-on-treatment for FOLFIRINOX was median 105 days (generally 1 st line), for gemcitabine/nab-paclitaxel was median 143 days (generally 2 nd line), and for all targeted therapies was median 106 days. Conclusions: XCELSIOR is an efficient nationwide observational research protocol designed to aggregate, structure, and analyze longitudinal clinical data. Application of this virtual platform to an emerging metastatic pancreatic adenocarcinoma dataset suggested biomarker-based molecular targeted therapies utilized at 3 rd and 4 th line have the potential to be efficacious. Further stratification and analyses will be performed as the data matures. Clinical trial information: NCT03793088.
High-intensity focused ultrasound (hifu) focal therapy for prostate cancer with mri-us fusion ablation navigation
Authors: C.H. Yee, P.K. Chiu, H.F. Wong, K.L. Lo, S.K. Yuen, M.H. Tam, C.K. Chan, J.Y. Teoh, C.F. Ng
Journal: European Urology (2022)
Predominance of BRCA2 mutation and estrogen receptor-positive breast cancer among BRCA1/2 mutation carriers.
Authors: Pascal Pujol, Kévin Yauy, Amandine Coffy, Nicolas Duforet-Frebourg, Sana Gabteni, Jean-Pierre Daurès, Frederique Madeleine Penault-Llorca, Laetitia Collet, Frédéric Thomas, Clare Turnbull, Virginie Galibert, Chloé Rideau, Benoit You, David Geneviève, Kevin S. Hughes, Nicolas Philippe
Journal: Journal of Clinical Oncology (2022)

551 Background: PARP inhibitor (PARPi) agents can improve progression-free survival of patients with breast cancer (BC) who carry a germline BRCA1 or BRCA2 pathogenic or likely pathogenic variant (gBRCA1/2) in both the metastatic and adjuvant setting. Therefore, we need to redefine the criteria of women and tumor phenotype that should be tested for gBRCA1/2. Methods: We studied the relative distribution of gBRCA1 and gBRCA2 in unselected populations of women with BC and in unaffected individuals. We also analyzed the proportion of estrogen receptor (ER)-positive (ER+) tumors in unselected BC patients with gBRCA1/2.We performed a meta-analysis of studies of unselected BC that analyzed the relative contribution of gBRCA1 versus gBRCA2 and ER+ tumors among gBRCA1/2 carriers. We then performed a meta-analysis of gBRCA1/2 carriage in unaffected individuals, from genome-wide population studies, the gnomAD databank, and case–control studies. Results: The BRCA2 gene was involved in 54% of BC in unselected patients with gBRCA1/2 (n=108,699) and 59% of unaffected individuals (n=238,973) as compared with 38% of gBRCA1/2 family cohorts (n=29,700). The meta-analysis showed that 1.66% (95% CI 1.08-2.54) and 1.71% (95% CI 1.33-2.2) of unselected BC patients carried a gBRCA1 and gBRCA2, respectively. In unaffected individuals, the frequency of heterozygosity for gBRCA1 and gBRCA2 was estimated at 1/434 and 1/288, respectively. Nearly 0.5% of unaffected individuals in the studied populations carried a gBRCA1/2. Carriage of a gBRCA was 2.5% for patients with ER+ tumors (95% CI 1.5-4.1) and 5.7% (95% CI 5.1-6.2) for those with ER- tumors. Overall, 58% of breast tumors occurring in women carrying a gBRCA1/2 were ER+ (n=86,870). Conclusions: This meta-analysis showed that gBRCA2 carriage is predominant in unselected BC and in unaffected individuals. ER+ tumors among women with gBRCA1/2-related BC is predominant and has been underestimated. Because PARPi agents improve progression-free survival with ER+ gBRCA1/2 BC in both the adjuvant and metastatic setting, BC should be considered regardless of ER status for BRCA1/2 screening for therapeutic purposes.
Clinical performance of Xpert Bladder Cancer test in patients with upper urinary tract cancer: Results and possibilities for future use
Authors: J.A. Rossi De Vermandois, V. Cellini, G. Manfredini, G. Maiolino, M. Marsico, E. Saqer, M. Vincenza, C. Rosy, G. Cochetti, E. Mearini
Journal: European Urology (2022)
Clinical characteristics, outcomes and survival of patients with metastatic colorectal cancer on phase I trials: A single center experience from 1999 to 2022.
Authors: M Bakri Hammami, Mohammad Haroon Ghalib, Radhashree Maitra, Ana Acuna-Villaorduna, Sanjay Goel
Journal: Journal of Clinical Oncology (2022)

e15593 Background: Metastatic colorectal cancer (mCRC) is a leading cause of cancer mortality. Few treatment options exist for patients who fail to respond to standard therapeutic agents. For patients with good performance status, phase I studies offer a valuable treatment option with a chance of clinical benefit. In this study, we report clinical characteristics, outcomes and survival of patients enrolled in phase I clinical trials at our institution. Methods: Medical records of patients with mCRC enrolled in phase I clinical trials between January 1999 to January 2022 at our institution were reviewed. Patient demographics, clinical characteristics, laboratory values, toxicities and survival time were analyzed. Overall survival (OS) was calculated as date of diagnosis of metastatic disease to death or last follow up. Phase 1 specific OS was analyzed from date of entry to first phase I trial to death. Results: 212 enrollments corresponding to 174 unique patients enrolled in 50 phase 1 clinical trials were reviewed. 53% (n = 112) were females with a median age of 60 years old [range 29-83]. 95% (n = 201) had an ECOG score of 0-1. The clinical benefit rate (stable disease plus partial response) was 35% and ORR was 4.3%. The median OS was 149 weeks, and the phase I OS was 23 weeks. Majority of the patients (53%, n = 110) received 3 or more lines of chemotherapy prior to phase I trial. In a univariable (UVA) model, the factors associated with better clinical outcome were WBC &lt; 10.8 (P &lt; 0.001), Hb &gt; 12 (p = 0.011), ECOG score 0 or 1 (p = 0.005), baseline AST &lt; 50 (p = 0.006), baseline albumin &gt; 3.5 (p &lt; 0.001), baseline LDH &lt; 305 (p &lt; 0.001). Conclusions: Phase I trials offer a reasonable option for patients with metastatic CRC. Our experience sheds light on the potential for improved outcomes in terms of survival. The survival of patients is at par with those used in late-stage disease including regorafenib and trifluridine/tipiracil. As expected, normal baseline lab parameters and better PS affect survival. Further modeling will be continued.
SWK-02. Palliative sedation in pediatric patients suffering from brain tumors: choosing the best drugs to improve end of life
Authors: Marta Podda, Elisabetta Schiavello, Carlo Alfredo Clerici, Veronica Biassoni, Fabio Simonetti, Maura Massimino
Journal: Neuro-Oncology (2022)

Abstract INTRODUCTION: For terminally-ill children with brain tumors care focuses on quality of life, and patient management fundamentally affects grieving families. We describe our experience of palliative sedation (PS) for children with refractory symptoms caused by solid tumors, focusing on BT (brain tumor). METHODS: Retrospective data on all children treated for cancer who died between 1/2016-12/2020 in our Institution were collected. RESULTS: Of the 29 patients eligible for the study, M/F 17/12, the median duration of disease was 12.5 months(range 3-51) and the median age at death was 8.5 years(range 1-22). Fifteen had BT (5 DIPG, 2 Ependymoma, 8 high-grade-glioma). The reasons for starting PS in BT were: seizures(5), central respiratory failure(6), locked-in-syndrome(1), decerebration(1). Midazolam was combined in 16 cases with other drugs (neuroleptics, alpha-2 agonists, antihistamines) to achieve adequate sedation. Ten/15 with BT received antiepileptic therapy, apart midazolam. BT patients received oral benzodiazepins before PS less frequently than those with other cancers (p = 0.0033). Throughout the period of PS and on the day of death, patients with BT were given lower doses of midazolam and morphine. Mean dose of midazolam was 0.027 mg/kg/h (range 0.0069-0.06) for patients with BT, 0.055 mg/kg/h (range 0.01-0.38) for the others, while the mean morphine doses were 0.048 mg/kg/h (range 0-0.08) and 0.09 mg/kg/h (range 0.013-0.13), respectively. CONCLUSIONS: BT patients require less intensive analgesic-sedative therapies because their already impaired state of consciousness. Optimizing pharmacological treatments demands a medical team that knows how drugs (even developed for other indications) work. Emotional-relational aspects are important too, any action to lower a patient’s consciousness should be explained to the family. Guidelines on PS in pediatrics could help, providing they acknowledge that any child’s death is always a unique case.
RARE-27. Treatment and outcomes in atypical choroid plexus papilloma: a single institution experience
Authors: Andrew Cluster, Evan Cantor, Ashley Meyer, Andrea Ogle, Sean McEvoy, Jennifer Strahle, Nicole Brossier, Margaret Shatara, David Limbrick, Mohamed Abdelbaki
Journal: Neuro-Oncology (2022)

Abstract BACKGROUND: Atypical choroid plexus papillomas (aCPP) are rare central nervous system (CNS) tumors often occurring in very young children. While surgical resection has been a mainstay of therapy, there is no consensus and limited data on the treatment of relapsed or metastatic tumors. METHODS: Retrospective review of the treatment and outcome of patients diagnosed with aCPP since 2011 was performed. RESULTS: Of the seven patients, 4 were male and 3 were female with a median age of 3 years at diagnosis (range: antenatal to 18 years old). All non-metastatic patients (six) were treated with surgery and all achieved gross total resection. Two patients had diffuse leptomeningeal contrast enhancement on diagnosis MRI that resolved after resection of primary tumor alone. One patient developed local relapse underwent re-resection with a GTR then was treated with 4 cycles of chemotherapy based on CPT-SIOP-2000 protocol (carboplatin, etoposide) and has not had further relapse in 24 months. One patient had metastatic disease at the time of diagnosis. They were treated with adjuvant chemotherapy, which stabilized disease for 36 months until they had progression. Additional four cycles were given and has again stabilized disease now 8 months from completion of that therapy. One non-metastatic patient died of unknown causes 28 months from diagnosis. CONCLUSIONS: Surgical resection remains the standard of care for patients with aCPP. However, chemotherapy based on the SIOP backbone may be useful to reduce the need for or to delay radiation therapy in select patients in the relapsed or metastatic setting.